Molecular pathology underlying the robustness of cancer stem cells
Autor: | Hideyuki Saya, Go J. Yoshida |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Medicine (General) Prrx1 Paired-related homeodomain transcription factor 1 GSH reduced glutathione medicine.medical_treatment Intratumoral heterogeneity Review ALDH Aldehyde dehydrogenase Targeted therapy 0302 clinical medicine NSCLC non–small cell lung cancer IL Interleukin HNSCC Head and neck squamous cell cancer CTC Circulating tumor cell Molecular pathology E/M Epithelial/mesenchymal ABC ATP-binding cassette DTC Disseminated tumor cell Nrf2 nuclear factor erythroid 2–related factor 2 OXPHOS Oxidative phosphorylation CD44 variant Phenotype MET mesenchymal-to-epithelial transition EGF Epidermal growth factor TGF-β Transforming growth factor–β EMT Epithelial-to-mesenchymal transition Plasticity Epithelial-to-mesenchymal transition (EMT) Biomedical Engineering CD44v CD44 variant CSC Cancer stem cell Biology Biomaterials 03 medical and health sciences R5-920 ECM Extracellular matrix Cancer stem cell Niche medicine Progenitor cell BMP Bone morphogenetic protein GSC Glioma stem cell Tumor microenvironment QH573-671 EpCAM Epithelial cell adhesion moleculeE CAF Cancer-associated fibroblast Robustness (evolution) HGF Hepatocyte growth factor Radiation therapy 030104 developmental biology Cancer research SRP1 Epithelial splicing regulatory protein 1 Cytology CagA Cytotoxin-associated gene A 030217 neurology & neurosurgery MAPK mitogen-activated protein kinase Developmental Biology ROS Reactive oxygen species |
Zdroj: | Regenerative Therapy Regenerative Therapy, Vol 17, Iss, Pp 38-50 (2021) |
ISSN: | 2352-3204 |
Popis: | Intratumoral heterogeneity is tightly associated with the failure of anticancer treatment modalities including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Such heterogeneity is generated in an evolutionary manner not only as a result of genetic alterations but also by the presence of cancer stem cells (CSCs). CSCs are proposed to exist at the top of a tumor cell hierarchy and are undifferentiated tumor cells that manifest enhanced tumorigenic and metastatic potential, self-renewal capacity, and therapeutic resistance. Properties that contribute to the robustness of CSCs include the abilities to withstand redox stress, to rapidly repair damaged DNA, to adapt to a hyperinflammatory or hyponutritious tumor microenvironment, and to expel anticancer drugs by the action of ATP-binding cassette transporters as well as plasticity with regard to the transition between dormant CSC and transit-amplifying progenitor cell phenotypes. In addition, CSCs manifest the phenomenon of metabolic reprogramming, which is essential for maintenance of their self-renewal potential and their ability to adapt to changes in the tumor microenvironment. Elucidation of the molecular underpinnings of these biological features of CSCs is key to the development of novel anticancer therapies. In this review, we highlight the pathological relevance of CSCs in terms of their hallmarks and identification, the properties of their niche—both in primary tumors and at potential sites of metastasis—and their resistance to oxidative stress dependent on system xc (−). Highlights • Intratumoral heterogeneity driven by CSCs is responsible for therapeutic resistance. • CTCs survive in the distant organs and achieve colonization, causing metastasis. • E/M hybrid cancer cells due to partial EMT exhibit the highest metastatic potential. • The CSC niche regulates stemness in metastatic disease as well as in primary tumor. • Activation of system xc(-) by CD44 variant in CSCs is a promising therapeutic target. |
Databáze: | OpenAIRE |
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